The use of deuterated phenylalanine for the in vivo assay of phenylalanine hydroxylase activity in children

Fifteen children, five with phenylketonuria (PKU), five with hyperphenylalaninaemia, and five phenotypically normal but at risk of being carriers for PKU, were given [ring²H₅]phenylalanine orally in amounts ranging from 75 mg/kg to 10 mg/kg. Plama was assayed for [²H₅]phenylalanine and [²H₄]tyrosine at hourly intervals, the amino acids being measured as the N-acetyl, n-propyl esters by gas chromatography-mass spectroscopy. The results obtained were calculated as the log of the ratio [²H₅]phenylalanine: [²H₄]tyrosine in the plasma. The five patients with PKU had ratios of infinity because no [²H₄]tyrosine was measured in their plasma during the experimental period. The patients with hyperphenylalaninaemia had log ratios over 2.00 throughout the assay period. Among the five normal children three are considered to be carriers for PKU as the logarithms of the [²H₅]phenylalanine: [²H₄]tyrosine ratios were 1.77, 1.73, and 1.33 and remained over 1.00 during the assay period. The other children had log ratios of 1.16 and 1.00 at the first hour which dropped below 1.00 subsequently, suggesting normal activity of phenylalanine hydroxylase.